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33
complaints, it is extremely important to correlate the atypical symptoms with the
reux episodes to justify invasive antireux therapies [10, 18–20].
Results of 24-h pH monitoring can be expressed in different ways. One option is
the expression as percentage of pH<4 during the measured time period. A border-
line has been determined between 4.5% and even as high as 6% for the pathologic
range above these values [14–17, 21].
Another option is the well-established DeMeester score with a borderline
between normal and pathologic at 14.7 score value [14, 15]. Other criteria have
been tried but have not been used very often. For the impedance evaluation, Table3.1
shows the available data. Shay etal. have analyzed 60 individuals to gain normal
values [16].
The median acid exposure in the distal esophagus (percentage acid exposure)
was in this analysis for the total time of measurement 1.6% (95th percentile: 5%).
In upright position, these data were 1.5% (6.2%) and supine 0.1% (5.3%).
As transnasal probes can be quite uncomfortable for the patients, wireless probes
and detection systems were developed such as the BRAVO™ system. The probe is
placed in the esophagus above the endoscopic visible Z-line or by measuring the
distance by manometry or by pH change, which would be less accurate. The advan-
tage of the system is the measurement only on one spot of the esophagus and only
acid assessment. The disadvantage is that the probe is not able to measure imped-
ance, which misses the weak acid and nonacid reux episodes.
Fig. 3.8 A 24-h-impedance-pH monitoring of esophagus and stomach of a patient with GERD
and a pathologic gastroesophageal reux (DeMeester score 41.8). The visual analysis shows that
most reux episodes occur during daytime in this patient
Table 3.1 Normal data for 24-h impedance-pH monitoring as published by Shay etal. [16]
Median/95th percentile
Total reux
Acid reux
pH<4
Weakly acid
pH4–7
Total 30/73 18/55 9/26
Upright 27/67 17/52 8/24
Supine 1/7 0/5 0/4
3 Diagnostic Investigations inGERD
34
High-Resolution Manometry (HRM)
Esophageal manometry is not important in establishing the diagnosis of GERD [10,
15, 22–26]. It does, however, have value as a marker of severity of the disease in that
incompetence of the LES is associated with more severe disease and long-term
progression [10, 15, 23]. Manometry studies are important prior to any surgical
procedure to evaluate motility disorders especially spastic motility disorders or
achalasia [10, 18, 19]. Furthermore, esophageal manometry is important for the
measurements of the lower esophageal sphincter (LES) position in order to place
the pH probes at the exact position 5cm above the LES upper border [10, 15].
High-resolution manometry (HRM) has improved the manometric diagnostic for
the esophagus substantially, since it is more easy for the patient and esophageal
motility can be classied in a more differentiated way [19] (Fig.3.9).
The indications for HRM are discussed sometimes controversially, since some
follow the idea that manometry is necessary for identifying the correct position of
the LES for pH probe placement, while others think this is not necessary and could
be done by pullback of the pH probe and wait for the pH change from intragastric
acidic values to esophageal levels. In most guidelines, it is requested or suggested
to perform an esophageal manometry before pH monitoring [10].
Physiologic transition zone in the
proximal esophagus
Pressure level of the
esophagogastric junction (EGJ)
composed of the LES and the
diaphragm
Relaxation of the LES following a
pharyngeal swallow of a water bolus
Deglutitive EGJ relaxation window
Fig. 3.9 Demonstration of a physiologic esophageal response to a swallow with normal peristalsis
and relaxation of the LES for a symptom-free passage of the bolus
D. C. Kunkel
35
Another important indication for HRM is the verication or exclusion of esopha-
geal motility disorders in GERD patients (Figs.3.10 and 3.11). This information is
especially important prior to interventional therapy and antireux surgery [10,
18, 19].
Conclusion
Further diagnostic investigations may be needed to verify functional abnormalities
and establish the indication for surgery or other invasive therapies. Investigations
that can evaluate the status of esophageal and gastric function include high-
resolution manometry.
HRM facilitates the procedure for the patients. Dynamic barium-sandwich vid-
eography is important to evaluate patients with dysphagia. In large hernias, a barium
study can provide information about the possibility of a short esophagus. In GERD
patients with nausea and vomiting as major complaint, gastric emptying studies and
duodeno-gastroesophageal reux assessment should be done to evaluate the pres-
ence of a gastroduodenal motility disorder such as delayed gastric emptying.
Endoscopy is especially important in exclusion of malignant disease and in the
presence of alarm symptoms such as dysphagia, retrosternal pain, and bleeding.
With endoscopy, it is possible to establish the diagnosis of GERD and its grade of
Fig. 3.10 HRM of a patient with GERD and hiatal hernia. The separation between LES and the
diaphragm is clearly demonstrated indicating also the weakness of the LES and the anatomical
alteration by the growing hiatal hernia
3 Diagnostic Investigations inGERD
36
severity, if reux esophagitis is present. If esophagitis is excluded, the presence of
NERD must be established using functional studies.
For diagnostic workup prior to surgery, endoscopy, 24-h pH monitoring, and
manometry are important for the optimal selection for patients. For the surgical
relevant pathophysiologic background, it is important to determine either the LES
incompetence by esophageal manometry or the increased incidence of transient
sphincter relaxations by sleeve manometry. Manometry prior to surgery is impor-
tant in order to exclude spastic esophageal motility disorders.
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© Springer Nature Switzerland AG 2020
S. Horgan, K.-H. Fuchs (eds.), Management of Gastroesophageal Reux Disease,
https://doi.org/10.1007/978-3-030-48009-7_4
Medical Therapy ofGERD
KarimaFarrag andJürgenStein
Introduction
In Western industrial societies, it is estimated that 10–15% of the population suffers
from gastroesophageal reux disease (GERD) [1–3]. Over the past three decades,
medical therapies have developed to the point where an overwhelming majority of
patients with mild to moderate symptoms of GERD can be quite successfully treated
[2, 4]. With a view to therapeutic decision-making, however, diagnosis may in some
cases be hindered by the wide diversity of symptoms associated with GERD
[2, 5–7].
The Montréal denition and classication of GERD describes and categorizes
different types of symptoms of GERD [2]. While heartburn and regurgitation are
specic symptoms of the disease that characterize the reux event quite clearly,
other symptoms such as nausea, vomiting, dysphagia, and chest pain, extraesopha-
geal symptoms such as cough or hoarseness, and other respiratory symptoms are
more difcult to relate to reux events [2]. Furthermore, the Montréal classication
differentiates symptoms into groups, such as the typical “reux syndrome” with
esophageal lesions, strictures, and reux or “reux and chest pain syndrome” or
“extraesophageal symptoms” such as laryngitis, cough syndrome, and even dental
erosions, possibly in association with pulmonary brosis, pharyngitis, and sinusitis.
Medical therapy can be applied in all these conditions. However, different syn-
dromes respond differently and may therefore require a more differentiated thera-
peutic approach [2, 4].
K. Farrag · J. Stein (*)
Department of Gastroenterology, Krankenhaus Sachsenhausen, Frankfurt am Main, Germany
e-mail: J.Stein@em.uni-Frankfurt.de
4
40
Lifestyle Intervention inGERD
Ingestion of alcohol has been shown to exacerbate reux symptoms by decreasing
the pressure of the lower esophageal sphincter (LES), increasing acid secretion
through gastrin stimulation, and decreasing esophageal motility [8, 9].
Furthermore, nonalcoholic carbonated beverages such as carbonated water and
caffeinated or caffeine-free cola have been shown to cause a short-term reduction in
the intraesophageal pH and a transient decrease in LES basal pressure and to
increase gastric acid secretion. In some cases, therefore, it may be benecial for the
patient to reduce or avoid their consumption [9, 10].
While tea and especially coffee consumption have previously been reported to be
associated with GERD, two recent meta-analyses failed to show a signicant rela-
tionship between tea and/or coffee consumption and the overall risk of GERD
[11, 12].
Along with diet, an important lifestyle component of GERD symptoms is the
timing of meals in relation to sleep. Dinner within 2–3hours of bedtime and snack-
ing after dinner were strongly associated with increased reux symptoms [8, 9, 13].
In order to reduce reux during sleep, it has been recommended to raise the head
end of the bed. Sleeping with a bedhead elevation achieved using 28cm blocks was
associated with faster acid clearing and fewer and shorter reux episodes. Moreover,
sleeping with a wedge pillow has also been associated with decreased esophageal
acid exposure. Such a strategy may be especially benecial in patients with late
evening or nocturnal GERD [8, 9].
Accumulating epidemiological data clearly suggest obesity to be among the root
causes of the GERD epidemic of the twenty-rst century. Not only does obesity
affect esophageal motility, but in patients with obesity, an increase in abdominal
pressure frequently causes the disruption of the gastroesophageal junction [13].
Both of these effects have sparked debate on obesity as a likely causative factor for
GERD.Not surprisingly, a weight loss of 10% was demonstrated to be associated
with signicantly decreased reux symptoms, i.e., heartburn, regurgitation, and
noncardiac chest pain. Therefore, the improvement or normalization of BMI is con-
sidered a rst step toward lifestyle modication in patients with obesity-related
GERD [8, 9].
As smoking has been shown to be implicated in the exacerbation of reux symp-
toms, cessation of smoking should also be recommended. Last but not least, patients
should be instructed to exercise regularly in order to strengthen the striated muscle
in the diaphragmatic crura, resulting in a stronger antireux barrier [8, 9].
Medical Therapy
While in the last century antacids were over many decades the best medical options
that were available, H2 blockers in the 1970s and the development of proton pump
inhibitors (PPI) in the 1980s have advanced the therapeutic success of medical
therapy substantially. The effectivity of PPIs compared to other medical agents has
K. Farrag and J. Stein
41
been shown in many randomized trials showing the healing of reux esophagitis
and reducing the major symptom of heartburn, when taken in adequate dosage and
sequence [2, 4, 14, 15]. The latter seems very important, and one cannot emphasize
this point enough for a successful therapy. Since GERD is a disease with a multi-
factorial background and a number of pathophysiologic components involved, it is
not surprising that the therapeutic response may vary from patient to patient. In
addition, there may be different therapeutic responses among patients depending
on different PPIs on the market as well as with different concepts of dosage
[2, 4, 15].
PPI therapy in the acute situation is a very effective treatment to compensate and
reduce the acute symptoms, mainly epigastric and thoracic pain and heartburn.
There is in this situation no role for any surgical treatment. There are many studies
showing the effect of PPIs in improving the patient’s symptoms and healing reux-
based esophagitis [2, 4, 15–20]. PPIs are the rst-line treatment. Dosage and dura-
tion of treatment can be individualized and depends on the patient’s status and
problems. PPIs are more effective than all the other available medical options [2, 15,
18–20]. The aim of the treatment is usually the reduction of reux esophagitis and
the reduction/stopping of the major symptoms such as heartburn, chest pain, or
epigastric pain.
There is a substantial discussion about that time of the rst endoscopy to verify
the diagnosis [2, 4, 15, 18–20]. According to most of the current guidelines, it is
suggested that an initial treatment of PPI can be administered in patients with this
suspicion for GERD and typical symptoms [2, 4, 11–15]. Especially if the initial
PPI therapy is successful, no urgent endoscopy or other diagnostics are needed.
However, in case of “alarm symptoms” such as bleeding or dysphagia, earlier diag-
nostic intervention is absolutely necessary [2, 4, 18–20].
The response to PPI therapy may differ depending on the individual patient and
also depending on differences in the status of GERD in a given patient. Several fac-
tors may play a role such as the degree of failure of the antireux barrier, a possible
failure of esophageal motility, and also a disorder in gastric emptying. Table4.1
demonstrates the overview on the acute therapy of GERD.Several guidelines have
expressed these actions to treat patients in the acute situation [2, 4, 18–20].
Long-term therapy of GERD is often necessary, since GERD is a chronic disease
[2, 18–22]. Frequently, patients are treated over more than 5 or 10years. This is
done in clinical practice despite the fact that the drug’s use is recommended usually
only for months. Since every day millions of patients take PPIs against symptoms in
the upper gastrointestinal tract, there should be, from the medical standpoint, some
strong inuence to push the evidence from guidelines for the indications for PPI
therapy [20]. Furthermore, GERD may have a mild to moderate clinical course, and
there is a clinical form of a progressive disease, causing functional and anatomical
alterations that will limit the success of medical therapy [21, 22].
PPIs are very successful for the majority of patients with GERD as a long-term
treatment, which has been shown by many large trials [2, 4, 16–18]. In randomized
controlled trials, this success of PPI therapy in adequate dosage is shown that typi-
cal reux symptoms can be stopped in 50–70% [2, 4, 16–18]. However,
4 Medical Therapy ofGERD
42
approximately 30% of patients under long-term PPI therapy were not completely
satised with their therapeutic result [16–18, 22]. These patients need diagnostic
workup to evaluate possibilities of a progressive form of disease which may be bet-
ter off with surgical therapy.
Table 4.2 demonstrates the effect of long-term treatment with PPI therapy apply-
ing adequate dosage and intake of the medication. A systematic analysis of the lit-
erature shows that healing of a mild-to-moderate reux esophagitis is almost always
successful by PPI therapy [2, 4, 16–20]. Healing rates in patients with severe reux
esophagitis are more limited, and a control of symptoms in these cases may be only
up to 75% success rate. Symptom control by PPI therapy in patients with extrae-
sophageal symptoms may be even worse [23–29].
Therefore, a differentiated diagnostic analysis of the precise background of the
disease in a given patient is important [30–34]. A limited success of PPI therapy is
very often due to an insufcient intake in sequence and dosage of the patient.
Patient’s compliance plays a major role in the insufciency of PPI therapy [2, 18].
As a consequence, this should be checked initially, when the patient complains
about insufcient treatment by PPI therapy, whether he or she follows the correct
instructions of intake.
Another reason for insufcient treatment and insufcient effect of PPI therapy
can be the multifactorial background and pathophysiology of GERD [4, 19–22,
35–38]. In a patient with severe mechanical incompetence of the lower esophageal
sphincter or in patients with severe alterations of esophageal and/or gastric motility,
a medical therapy may be limited [19–22, 35].
Table 4.1 Therapy of GERD in the acute situation
Indication
Drugs Dosage
Duration
Reux symptoms:
Heartburn
Regurgitation
Antacids
PPI±alginate
Standard dosage:
Omeprazole 20mg
Lansoprazole 30mg
Rabeprazole 20mg
Pantoprazole 40mg
Esomeprazole 40mg
4weeks
NERD PPI±alginate
Antacids
H
2
-blockers
Standard dosages 4weeks
Esophagitis
Los Angeles A, B
PPI Standard dosage 4–6weeks
Esophagitis
Los Angeles C, D
PPI Standard dosage
Up to double
1-0-1
Minimum 8weeks
Often long term
Esophageal stricture PPI Double standard dosage
1-0-1
Long term
Chest pain and
reux
PPI Double standard dosage
1-0-1
Testing 2weeks
8weeks
Extraesophageal
symptoms
PPI+alginate Double standard dosage
1-0-1
4weeks
Barrett’s esophagus PPI Depending on esophagitis
and present symptoms
Depending on esophagitis
and present symptoms
K. Farrag and J. Stein